The central research theme of the Mayo Clinic Specialized Center of Research (SCOR) in Urolithiasis is to examine the factors that promote and prevent crystal growth within the urinary tract in order to further understand the mechanisms that allow stone formation and to improve treatment to prevent this complication. The specific objectives of the Mayo Clinic SCOR in Urolithiasis are: 1) to examine sites of reabsorption and secretion of the major ion species within the nephron; 2) to better define the relative roles of supersaturation, inhibitor activity, matrix and epitaxy in animal models and patients with calcium urolithiasis; 3) to measure the effect of therapy on the multiple factors involved in crystal growth in the urine of patients actively forming stones in the urinary tract; 4) to identify abnormalities caused by stone producing stresses that result in urolithiasis in some patients as well as prestress abnormalities that may allow the formation of a stone within the urinary tract; and 5) to study in a systematic way the epidemiology and genetics of urolithiasis in a well defined population base.